Archaeal Genome Guardians Give Insights into Eukaryotic DNA Replication and Damage Response Proteins
Figure 5
Conservation of MR family members in three domains. (a) Structures of bacterial homologs have elucidated domain organization of MR components. The bacterial Mre11 dimer, exemplified by the T. maritima homolog (PDB code 2Q8U), contains the larger, N-terminal nuclease domains (green), the adjacent capping domains, and Rad-family member binding domains (not structurally defined for TmMre11). The Rad50 portion of the Mre11-Rad50 complex (PDB code 3THO) in T. maritima is comprised of a curved, globular domain of two lobes with intervening coiled coils (lower regions). (b) Human and yeast MRN structures reveal eukaryote-specific features. The subunit orientation of human Mre11 dimer (PDB 3T1I) is substantially rotated, as compared to other known homolog structures. Mre11 and Nbs1 complexes exemplified by S. pombe (PDB codes 4FCX (SpMre11); 4FBW (SpMre11 with SpNbs1 C-terminal region); 3HUE (C-terminally truncated SpNbs1); 3HUF (SpNbs1 in complex with CTP1 peptide)) have revealed key regulatory interactions including the binding site of the Nbs1 C-terminal tail on Mre11 and the FHA domain interaction of Nbs1 with a phosphopeptide of CTP1. (c) Insights from archaeal MR components and complexes. Mre11 structures from P. furiosus (PDB codes I117 (PfMre11); 3DSC (PfMre11 with DNA); 3QKT (PfRad50 core); 3QKU (PfRad50 core with PfMre11 C-termini); 3QKS, 3QKR (PfRad50 subunits with PfMre11 C-termini); 1L8D (PfRad50 coiled coil and Zn hook)) have revealed DNA binding and partner interaction sites key to MR assembly. Likewise, complementary M. jannaschii structures have confirmed key architecture and interaction sites between MjMre11 and MjRad50 (PDB codes 3AUZ (MjMre11); 3AUX (MjRad50 core); 3AV0(MjRad50 core with MjMre11)).
